Abstract
Motivation
Genome-wide association studies (GWAS) are a powerful method to detect even weak associations between variants and phenotypes; however, many of the identified associated variants ...are in non-coding regions, and presumably influence gene expression regulation. Identifying potential drug targets, i.e. causal protein-coding genes, therefore, requires crossing the genetics results with functional data.
Results
We present a novel data integration pipeline that analyses GWAS results in the light of experimental epigenetic and cis-regulatory datasets, such as ChIP-Seq, Promoter-Capture Hi-C or eQTL, and presents them in a single report, which can be used for inferring likely causal genes. This pipeline was then fed into an interactive data resource.
Availability and implementation
The analysis code is available at www.github.com/Ensembl/postgap and the interactive data browser at postgwas.opentargets.io.
Streptococcus mitis is the closest relative of the major human pathogen S. pneumoniae. The 2,15 Mb sequence of the Streptococcus mitis B6 chromosome, an unusually high-level beta-lactam resistant and ...multiple antibiotic resistant strain, has now been determined to encode 2100 genes. The accessory genome is estimated to represent over 40%, including 75 mostly novel transposases and IS, the prophage phiB6 and another seven phage related regions. Tetracycline resistance mediated by Tn5801, and an unusual and large gene cluster containing three aminoglycoside resistance determinants have not been described in other Streptococcus spp. Comparative genomic analyses including hybridization experiments on a S. mitis B6 specific microarray reveal that individual S. mitis strains are almost as distantly related to the B6 strain as S. pneumoniae. Both species share a core of over 900 genes. Most proteins described as pneumococcal virulence factors are present in S. mitis B6, but the three choline binding proteins PcpA, PspA and PspC, and three gene clusters containing the hyaluronidase gene, ply and lytA, and the capsular genes are absent in S. mitis B6 and other S. mitis as well and confirm their importance for the pathogenetic potential of S. pneumoniae. Despite the close relatedness between the two species, the S. mitis B6 genome reveals a striking X-alignment when compared with S. pneumoniae.
Post-transcriptional regulation by small RNAs (sRNAs) in bacteria is now recognized as a wide-spread regulatory mechanism modulating a variety of physiological responses including virulence. In ...Streptococcus pneumoniae, an important human pathogen, the first sRNAs to be described were found in the regulon of the CiaRH two-component regulatory system. Five of these sRNAs were detected and designated csRNAs for cia-dependent small RNAs. CiaRH pleiotropically affects β-lactam resistance, autolysis, virulence, and competence development by yet to be defined molecular mechanisms. Since CiaRH is highly conserved among streptococci, it is of interest to determine if csRNAs are also included in the CiaRH regulon in this group of organisms consisting of commensal as well as pathogenic species. Knowledge on the participation of csRNAs in CiaRH-dependent regulatory events will be the key to define the physiological role of this important control system.
Genes for csRNAs were predicted in streptococcal genomes and data base entries other than S. pneumoniae by searching for CiaR-activated promoters located in intergenic regions that are followed by a transcriptional terminator. 61 different candidate genes were obtained specifying csRNAs ranging in size from 51 to 202 nt. Comparing these genes among each other revealed 40 different csRNA types. All streptococcal genomes harbored csRNA genes, their numbers varying between two and six. To validate these predictions, S. mitis, S. oralis, and S. sanguinis were subjected to csRNA-specific northern blot analysis. In addition, a csRNA gene from S. thermophilus plasmid pST0 introduced into S. pneumoniae was also tested. Each of the csRNAs was detected on these blots and showed the anticipated sizes. Thus, the method applied here is able to predict csRNAs with high precision.
The results of this study strongly suggest that genes for small non-coding RNAs, csRNAs, are part of the regulon of the two-component regulatory system CiaRH in all streptococci.
Abstract
The Ensembl (https://www.ensembl.org) is a system for generating and distributing genome annotation such as genes, variation, regulation and comparative genomics across the vertebrate ...subphylum and key model organisms. The Ensembl annotation pipeline is capable of integrating experimental and reference data from multiple providers into a single integrated resource. Here, we present 94 newly annotated and re-annotated genomes, bringing the total number of genomes offered by Ensembl to 227. This represents the single largest expansion of the resource since its inception. We also detail our continued efforts to improve human annotation, developments in our epigenome analysis and display, a new tool for imputing causal genes from genome-wide association studies and visualisation of variation within a 3D protein model. Finally, we present information on our new website. Both software and data are made available without restriction via our website, online tools platform and programmatic interfaces (available under an Apache 2.0 license) and data updates made available four times a year.
Abstract
The Ensembl project has been aggregating, processing, integrating and redistributing genomic datasets since the initial releases of the draft human genome, with the aim of accelerating ...genomics research through rapid open distribution of public data. Large amounts of raw data are thus transformed into knowledge, which is made available via a multitude of channels, in particular our browser (http://www.ensembl.org). Over time, we have expanded in multiple directions. First, our resources describe multiple fields of genomics, in particular gene annotation, comparative genomics, genetics and epigenomics. Second, we cover a growing number of genome assemblies; Ensembl Release 90 contains exactly 100. Third, our databases feed simultaneously into an array of services designed around different use cases, ranging from quick browsing to genome-wide bioinformatic analysis. We present here the latest developments of the Ensembl project, with a focus on managing an increasing number of assemblies, supporting efforts in genome interpretation and improving our browser.
Abstract
The Ensembl project (https://www.ensembl.org) makes key genomic data sets available to the entire scientific community without restrictions. Ensembl seeks to be a fundamental resource ...driving scientific progress by creating, maintaining and updating reference genome annotation and comparative genomics resources. This year we describe our new and expanded gene, variant and comparative annotation capabilities, which led to a 50% increase in the number of vertebrate genomes we support. We have also doubled the number of available human variants and added regulatory regions for many mouse cell types and developmental stages. Our data sets and tools are available via the Ensembl website as well as a through a RESTful webservice, Perl application programming interface and as data files for download.
PDF
